ZRANB3 is a structure-specific ATP-dependent endonuclease involved in replication stress response.
AffiliationDNA Damage Response Group, Paterson Institute for Cancer Research, University of Manchester, Manchester M20 4BX, United Kingdom.
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AbstractTo efficiently duplicate their genomic content, cells must overcome DNA lesions that interfere with processive DNA replication. These lesions may be removed and repaired, rather than just tolerated, to allow continuity of DNA replication on an undamaged DNA template. However, it is unclear how this is achieved at a molecular level. Here we identify a new replication-associated factor, ZRANB3 (zinc finger, RAN-binding domain containing 3), and propose its role in the repair of replication-blocking lesions. ZRANB3 has a unique structure-specific endonuclease activity, which is coupled to ATP hydrolysis. It cleaves branched DNA structures with unusual polarity, generating an accessible 3'-OH group in the template of the leading strand. Furthermore, ZRANB3 localizes to DNA replication sites and interacts with the components of the replication machinery. It is recruited to damaged replication forks via multiple mechanisms, which involve interactions with PCNA, K63-polyubiquitin chains, and branched DNA structures. Collectively, our data support a role for ZRANB3 in the replication stress response and suggest new insights into how DNA repair is coordinated with DNA replication to maintain genome stability.
CitationZRANB3 is a structure-specific ATP-dependent endonuclease involved in replication stress response. 2012, 26 (14):1558-72 Genes Dev
JournalGenes & Development
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- Authors: Ciccia A, Nimonkar AV, Hu Y, Hajdu I, Achar YJ, Izhar L, Petit SA, Adamson B, Yoon JC, Kowalczykowski SC, Livingston DM, Haracska L, Elledge SJ
- Issue date: 2012 Aug 10
- Structural insights into the function of ZRANB3 in replication stress response.
- Authors: Sebesta M, Cooper CDO, Ariza A, Carnie CJ, Ahel D
- Issue date: 2017 Jun 16
- Replication Fork Slowing and Reversal upon DNA Damage Require PCNA Polyubiquitination and ZRANB3 DNA Translocase Activity.
- Authors: Vujanovic M, Krietsch J, Raso MC, Terraneo N, Zellweger R, Schmid JA, Taglialatela A, Huang JW, Holland CL, Zwicky K, Herrador R, Jacobs H, Cortez D, Ciccia A, Penengo L, Lopes M
- Issue date: 2017 Sep 7
- Identification of a Substrate Recognition Domain in the Replication Stress Response Protein Zinc Finger Ran-binding Domain-containing Protein 3 (ZRANB3).
- Authors: Badu-Nkansah A, Mason AC, Eichman BF, Cortez D
- Issue date: 2016 Apr 8
- Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability.
- Authors: Poole LA, Cortez D
- Issue date: 2017 Dec